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Molecular mechanism of cancer chemoprevention by anthocyanins

花青素化学预防癌症的分子机制

基本信息

批准号：
13660130
负责人：
HOU De-xing
金额：
$ 2.24万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

项目摘要

Anthocyanidins are the aglycon nucleuses of anthocyanins, which are reddish pigments widely spread in colored fruits and vegetables. To investigate the anti-cancer effect of anthocyanins, induction of apoptosis was tested in human promyelocytic leukemia cells (HL-60), which is a valid model for testing antileukemic or general antitumoral compounds. Of six anthocyanidins representing the aglycons of most of anthocyanins, only those with an ortho-dihydroxyphenyl structure on the B-ring induce apoptosis, suggesting that the ortho-dihydroxyphenyl structure of anthocyanidins may contribute to the induction of apoptosis. Delphinidin, the most potent inducer, causes apoptosis in a time-and dose-dependent manner. The efficacious induction of apoptosis was observed at 100 μM for 6 h. Concomitant with the apoptosis, delphinidin stimulates JNK pathway activation including JNK phosphorylation and c-jun gene expression, and activates caspase-3. Antioxidants including N-acetyl-L-cysteine (NAC) and catalase effectively block delphinidin-induced JNK phosphorylation, caspase-3 activation, and DNA fragmentation. Moreover, anthocyanidins directly cause HL-60 cells to generate intracellular hydrogen peroxide. Thus, anthocyanidins may trigger an apoptotic death program through an oxidative stress-involved JNK signaling pathway. The induction of apoptosis by anthocyanins may be the pivotal mechanism by which its chemopreventive action against cancer is based.

花青素是花青素的糖基核，是一种广泛存在于有色水果和蔬菜中的红色色素。为了研究花青素的抗癌作用，我们在人早幼粒细胞白血病细胞（HL-60）中进行了诱导细胞凋亡的实验，这是检测抗白血病或一般抗肿瘤化合物的有效模型。在代表大多数花青素苷元的6种花青素中，只有在b环上具有邻二羟基苯基结构的花青素能诱导细胞凋亡，提示花青素的邻二羟基苯基结构可能有助于诱导细胞凋亡。飞燕草苷是最有效的诱导剂，其诱导细胞凋亡具有时间和剂量依赖性。在100 μM作用6 h，可有效诱导细胞凋亡。在细胞凋亡的同时，飞鸽苷刺激JNK通路活化，包括JNK磷酸化和c-jun基因表达，并激活caspase-3。抗氧化剂包括n-乙酰- l-半胱氨酸（NAC）和过氧化氢酶能有效阻断飞鸽苷诱导的JNK磷酸化、caspase-3激活和DNA断裂。此外，花青素直接导致HL-60细胞产生细胞内过氧化氢。因此，花青素可能通过与氧化应激相关的JNK信号通路触发细胞凋亡程序。花青素诱导细胞凋亡可能是其化学预防癌症作用的关键机制。